Title: Development of Piezoresistive Microcantilever based Force Feedback
System for Study of Mechanotransduction in C. elegans
University Oral Examination
Sung-Jin Park
Department of Mechanical Engineering
Stanford University
Advisor: Beth Pruitt and Miriam Goodman
Date: Monday, March 16, 2009
Time: 10AM (Refreshments served at 9:45AM)
Location: Building 300- room 300 (Auditorium) (map attached)
<http://campus-map.stanford.edu/index.cfm?ID=04-055>
Abstract:
Cellular mechanotransduction, the conversion of force into to an electrical
or biochemical signal, is a fundamental process essential to normal life,
including hearing, touch and balance. Among these, touch sensation is the
least understood. The nematode *Caenorhabditis elegans *is one of the most
powerful model organisms in which to analyze the mechanism of touch
sensation. Few techniques exist to provide forces and displacements
appropriate for such studies. To address this technological gap, we
developed a metrology using piezoresistive cantilevers as force-displacement
sensors coupled to feedback system in order to apply and maintain defined
load profiles to micron-scale animals. This thesis presents 1) design and
optimization of piezoresistive cantilever, 2) integration and development of
force clamp system, and 3) biological studies of *C.
elegans*mechanotransduction.
We developed and validated an analytical model to predict the force
sensitivity and force resolution of a piezoresistive cantilever. We
systematically analyzed the effects of process parameters on the sensitivity
and resolution of the cantilevers to optimize their design. This
optimization technique produced optimal cantilever with minimum resolution
such as 69 pN at 1-1000 Hz bandwidth. This analytical model and optimization
technique are very useful to design piezoresistive devices with complex
design conditions for biological applications.
We conducted biological studies of *C. elegans* mechanotransduction by
integrating the developed force probe with force and displacement feedback
system. We measured body stiffness of wild type and mutants which alter body
shape and cuticle proteins. The analysis of *C. elegans* body mechanics
suggests that shell mechanics dominates stiffness rather than hydrostatic
pressure. We also conducted the behavioral response of *C. elegans* to touch
stimuli by utilizing the system in force-clamping mode. We applied a 100 nN
to 10 mN force to freely-moving wild type and *mec-4* mutant which has loss
of touch receptor neuron. The behavioral result agrees with our prior
in-vivo work which suggests that electrical responses of wild type to touch
saturate near a force threshold, between 100nN and 1mN. These studies form a
part of the bigger puzzle of how body mechanics affect locomotion and force
sensing.
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